Ranolazine Unveiled: Rediscovering an Old Solution in a New Light
Giulia Azzurra De SantisTommaso De FerrariFrancesca ParisiMarco FranzinoAgustin Ezequiel MolineroAlessandro Di CarloLorenzo PistelliGiampaolo VettaAntonio ParlavecchioMarco TorreM ParolloG. MansiPietro Paolo TamborrinoA CanuG GrifoniLuca SegretiAndrea Di CoriStefano VianiGiulio Zucchelli
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Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine's mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies.Keywords:
Ranolazine
To review the pharmacology, pharmacokinetics, and clinical efficacy of ranolazine for the treatment of chronic stable angina.MEDLINE was searched (1966-February 2006) using the English-language key terms ranolazine and chronic stable angina. Additional studies were identified from the bibliographies of the reviewed literature.Studies evaluating ranolazine, alone or in combination with other agents, were incorporated in this review.Ranolazine is a metabolic modulator designed to improve cardiac energy availability and cardiac metabolism. It is believed to be a partial fatty acid oxidation inhibitor. Ranolazine has been shown to improve exercise duration and time to anginal attacks without significantly affecting heart rate or blood pressure. Adverse effects of ranolazine are reported to be dose related. The elimination half-life of ranolazine is estimated to be between 1.4 and 1.9 hours for the immediate-release and 7 hours for sustained-release preparations.Ranolazine has a unique mechanism of action that is different from that of conventional agents. It has been studied as monotherapy or in combination with other commonly prescribed agents. It appears that ranolazine has a promising safety data profile and does not affect hemodynamic parameters. At this point, although ranolazine should not be used in place of conventional therapy, it appears that ranolazine may be considered in the management of symptomatic patients when standard antianginal medications are not tolerated or are ineffective.
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Ranolazine is a novel anti-anginal agent.The mechanism of anti-angina pectoris may be related to the inhibition of the late Na~+ current in cardiac myocytes and the improvement of energy metabolism. Clinical studies showed that ranolazine might increase exercise tolerance,decrease anginal attacks and nitroglycerin consumption.
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Antiarrhythmic medications for the treatment of atrial fibrillation (AF) have limited efficacy and rare but potentially life-threatening side effects. Ranolazine is an antianginal agent that may have antiarrhythmic activity in AF.Using the Duke Enterprise Data Unified Content Explorer database, we analysed a cohort of AF patients on ranolazine. Patients served as their own historic control. Electrocardiograms (ECGs) were analysed before and after ranolazine initiation to determine the effect of ranolazine on dominant frequency (DF), f-wave amplitude, and organizational index (OI). We identified 15 patients with ECGs in AF before and after ranolazine. Ranolazine was associated with lower DF by an average of 10% (5.10 ± 0.74 vs. 5.79 ± 0.96 Hz, P = 0.04) but not with changes in OI (0.47 ± 0.11 vs. 0.50 ± 0.12, P = 0.71) or amplitude (0.47 ± 0.43 vs. 0.41 ± 0.40 mV, P = 0.82). Ranolazine was also associated with lower DF in patients (n = 10) not on concomitant antiarrhythmic therapy (5.25 ± 0.78 vs. 6.03 ± 0.79 Hz, P = 0.04).Ranolazine is associated with lower AF DF but no change in OI or fibrillatory wave amplitude. Prospective trials are needed to evaluate ranolazine's potential as a novel antiarrhythmic drug for AF.
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The paper presents the study of a new anti-anginal drug - sodium channel inhibitor ranolazine. Considered antianginal, anti-ischemic effect of the drug. Described reduction in angina attacks, increased exercise tolerance and quality of life of patients with stable angina during treatment with ranolazine. Discusses indications, contraindications, side effects, as well as the major clinical trials of the drug ranolazine in patients with coronary heart disease.
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The interactions of ranolazine, a new antianginal compound, with inhibitors and substrates of the CYP3A isoenzyme family were studied in 1 open-label and 4 double-blind, randomized, multiple-dose studies. In healthy adult volunteers, the authors sought (1) to determine the steady-state pharmacokinetics, safety, and tolerability of immediate- and sustained-release ranolazine with and without ketoconazole, diltiazem, or simvastatin and (2) to evaluate the effect of ranolazine on the pharmacokinetics of diltiazem, simvastatin, simvastatin metabolites, and HMG-CoA reductase activity. Ketoconazole increased ranolazine plasma concentrations and reduced the CYP3A4-mediated metabolic transformation of ranolazine, confirming that CYP3A4 is the primary metabolic pathway for ranolazine. Diltiazem reduced oral clearance of ranolazine in a dose-dependent manner. Simvastatin did not affect ranolazine pharmacokinetics, although ranolazine increased the AUC and C(max) of simvastatin, simvastatin acid, 2 simvastatin metabolites, and HMG-CoA reductase activity by <2-fold. Administration of ranolazine in combination with diltiazem or simvastatin was safe and well tolerated during the interval studied.
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Ranolazine is a new cardiovascular drug,whose mechanism is related to the inhibition of late Na + current in cardiac myocytes.Clinical studies showed that ranolazine could increase exercise tolerance,decrease anginal attacks and nitroglycerin consumption.Ranolazine also has the anti-arrhythmic effects and may improve cardiac systolic and diastolic function.
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Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward current. Moreover, ranolazine has other metabolic features which makes it effective in other diseases as well as coronary artery ones. In this paper I make an updated review of all possible therapeutic roles of ranolazine: through cardiology and beyond.
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Abstract Background This study set out to look at how naringenin affected the pharmacokinetics of ranolazine in rats. The pharmacokinetic investigation of ranolazine in rats following oral administration of ranolazine with or without coadministration of naringenin was successfully conducted using the established technique. Animals were administered the same medications for 7 days as part of a multiple dosage study (MDS), and the amount of ranolazine in plasma was calculated on 18 days. The intestinal transit of ranolazine in the presence and absence of naringenin and verapamil was examined in an in vitro experiment using the intestinal sacs of rats and chickens (P-glycoprotein inhibitor). Results Naringenin raised the maximal level (Cmax) of ranolazine from 231 ± 10.16 to 303.67 ± 9.46 and 325.67 ± 21.81 ng/mL in SDS and MDS, respectively. Moreover, naringenin elevated the area under the curve (AUC) of ranolazine from 1293.54 ± 37.18 to 1505.38 ± 100.30 and 1575.42 ± 76.98 ng/mL/h in SDS and MDS. In the presence of naringenin, there was an increase in the transfer of ranolazine from the mucosal side to the serosal side. Naringenin inhibits the enzymes Cytochrome P450 (3A4) or (CYP3A4) and P-glycoprotein (P-gp). The findings showed that naringenin might have a considerable impact on ranolazine pharmacokinetics, including extending its t 1/2 and raising its AUC. Conclusions The findings of the study showed that naringenin inhibits the enzymes CYP3A4 and P-gp. Therefore, naringenin might have a considerable impact on ranolazine pharmacokinetics, including extending its t 1/2 and raising its AUC. Graphical abstract
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Ranolazine is a novel new antianginal agent currently under investigation as monotherapy and adjunct therapy for the treatment of chronic stable angina. While the mechanism of action of ranolazine is not completely understood, it is believed to involve a reduction in fatty acid oxidation, ultimately leading to a shift in myocardial energy production from fatty acid oxidation to glucose oxidation. Since the oxidation of glucose requires less oxygen than the oxidation of fatty acids, ranolazine can help maintain myocardial function in times of ischemia. In addition, ranolazine has minimal effect on blood pressure and heart rate. Ranolazine, by inhibiting cellular ionic channels, prolongs the corrected QT interval. However, ranolazine has not yet been associated with any incidences of ventricular arrhythmia. The clinical data with ranolazine focuses on its use in chronic stable angina, where it has been shown to increase exercise tolerance and decrease angina compared with placebo, as well as in combination with beta-blockers and calcium channel blockers. The use of ranolazine for other cardiac conditions and the effect of ranolazine on morbidity and mortality remains to be determined. Ongoing clinical trials will help further establish the role of ranolazine in the treatment of cardiovascular disorders.
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Background Ranolazine is a new anti-anginal agent that inhibits abnormal late sodium currents, indirectly causing a decrease in diastolic cardiomyocyte calcium levels. This produces an energy-sparing effect and stabilizes cardiac membranes. Ranolazine has been shown to be a potent inhibitor of triggered activity in the experimental setting. Methods This case report describes the dramatic antiarrhythmic effects of ranolazine in a patient with highly symptomatic complex ventricular ectopy, including non-sustained ventricular tachycardia (NSVT). Cardiac ischemia and left ventricular systolic dysfunction were ruled out by cardiac catheterization. After failing standard treatment, we initiated ranolazine therapy. Results Ranolazine was effective in suppressing ectopic ventricular activity and completely suppressed NSVT. Conclusions Further research on the anti-arrhythmic properties of ranolazine in the clinical setting is needed.
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